Single-stage Open Lobectomy and Modified Ravitch Procedure in an Infant with Coexisting Severe Pectus Excavatum and Congenital Cystic Adenomatous Malformation.

ABSTRACT: Coexisting congenital cystic adenomatous malformation of the lungs and severe pectus excavatum (PE) is an uncommon presentation that poses significant management challenges. Conventionally managed in a staged manner, there are increasing reports of superior outcomes with single-staged concurrent repair with minimally invasive techniques (video-assisted thoracoscopic surgery [VATS] and minimally invasive repair of PE [MIRPE]). The outcome of a single-stage open repair for both anomalies has not been previously reported to the best of our search. We report the successful single-stage management of a 9-month-old infant with both anomalies who had an open lobectomy and modified Ravitch procedure. We aim to report the feasibility and safety of a single-stage concurrent repair of both conditions using open techniques, as VATS and MIRPE are not readily available in our environment.

[Application of Fetal Magnetic Resonance Imaging in Prognosis Assessment of Fetuses With Congenital Pulmonary Cystic Diseases]. / äº§å‰ç£å ±æŒ¯åœ¨å ˆå¤©æ€§è‚ºå›Šæ€§ç–¾ç— èƒŽå„¿é¢„åŽè¯„ä¼°ä¸­çš„åº”ç”¨ç ”ç©¶.

Objective: The aim of this study is to explore the practical value of prenatal magnetic resonance imaging (MRI) in the assessment of congenital cystic lung disease in fetuses, to evaluate the relative size of the lesion and the status of lung development, and to make an attempt at utilizing the strength of MRI in post-processing to obtain assessment indicators of the size of the lesion and the status of lung development, with which predictions can be made for the prognosis that these fetuses may face after birth. We retrospectively collected and analyzed the data of fetuses diagnosed with congenital cystic lung disease. Prenatal ultrasound examination of these fetuses led to the diagnosis that they were suspected of having congenital cystic lung disease and the diagnosis was confirmed by subsequent prenatal MRI. The fetuses were followed up to track their condition at birth (postnatal respiratory distress, mechanical ventilation, etc.), whether the fetuses underwent surgical treatment, and the recovery of the fetuses after surgical treatment. The recovery of the fetuses was followed up to explore the feasibility of prenatal MRI examination to assess fetal congenital pulmonary cystic disease, and to preliminarily explore the predictive value of prenatal MRI for the prognosis of fetuses with congenital pulmonary cystic disease. Methods: MRI fetal images were collected from pregnant women who attended the West China Second University Hospital of Sichuan University between May 2018 and March 2023 and who were diagnosed with fetal congenital pulmonary cystic disease by prenatal ultrasound and subsequent MRI. Fetal MRI images of congenital cystic lung disease were post-processed to obtain the fetal lung lesion volume, the fetal affected lung volume, the healthy lung volume, and the fetal head circumference measurements. The signal intensity of both lungs and livers, the lesion volume/the affected lung volume, the lesion volume/total lung volume, the cystic volume ratio (CVR), and the bilateral lung-liver signal intensity ratio were measured. The feasibility and value of MRI post-processing acquisition indexes for evaluating the prognosis of fetuses with congenital cystic lung disease were further analyzed by combining the follow-up results obtained 6 months after the birth of the fetus. Logistic regression models were used to quantify the differences in maternal age, gestational week at the time of MRI, CVR, and bilateral lung-to-liver signal intensity ratio, and to assess whether these metrics correlate with poor prognosis. Receiver operating characteristic (ROC) curves were used to assess the value of the parameters obtained by MRI calculations alone and in combination with multiple metrics for predicting poor prognosis after birth. Results: We collected a total of 67 cases of fetuses diagnosed with congenital cystic lung disease by fetal MRI between May 2018 and March 2023, and excluded 6 cases with no normal lung tissue in the affected lungs, 11 cases of fetal induction, and 3 cases of loss of pregnancy. In the end, 47 cases of fetuses with congenital cystic lung disease were included, of which 30 cases had a good prognosis and 17 cases had a poor prognosis. The difference in the difference between the signal intensity ratios of the affected and healthy sides of the lungs and livers of the fetuses in the good prognosis group and that in the poor prognosis group was statistically significant (P<0.05), and the signal intensity ratio of the healthy side of the lungs and livers was higher than the signal intensity ratio of the affected side of the lungs and livers. Further analysis showed that CVR (odds ratio [OR]=1.058, 95% confidence interval [CI]: 1.014-1.104), and the difference between the lung-to-liver signal intensity ratios of the affected and healthy sides (OR=0.814, 95% CI: 0.700-0.947) were correlated with poor prognosis of birth in fetuses with congenital cystic lung disease. In addition, ROC curve analysis showed that the combined application of lesion volume/affected lung volume and the observed difference in the signal intensity ratio between the affected and healthy lungs and liver predicted the prognosis of children with congenital cystic lung disease more accurately than the single-parameter judgment did, with the area under the curve being 0.988, and the cut-off value being 0.33, which corresponded to a sensitivity of 100%, a specificity of 93.3%, and a 95% CI of 0.966-1.000. Conclusions: Based on the MRI of fetuses with congenital cystic lung disease, we obtained information on lesion volume, lesion volume/affected lung volume, lesion volume/total lung volume, CVR, and bilateral lung-to-liver signal intensity ratio difference, all of which showing some clinical value in predicting the poor prognosis in fetuses with congenital cystic lung disease. Furthermore, among the combined indexes, the lesion volume/affected lung volume and bilateral lung-to-liver signal intensity ratio difference are more effective predictors for the poor prognosis of fetuses with congenital cystic lung disease, and show better efficacy in predicting the poor prognosis of fetuses with congenital cystic lung disease. This provides a new and effective predictive method for further assessment of pulmonary lung development in fetuses with congenital cystic lung disease, and helps improve the assessment and prediction of the prognosis of fetuses with congenital cystic lung disease.

The ten-year evaluation of clinical characteristics in congenital lung anomaly in pediatrics; a retrospective study in North of Iran.

INTRODUCTION: Congenital lung anomalies (CLA) are a group of anomalies, including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestrations (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts (BC). The prevalence of these rare anomalies has risen in recent years, according to various population-based studies due to advances in fetal ultrasound technology. METHOD: This retrospective study examines the diagnosis of CLA, and was conducted on 72 patients between March 2014 and March 2024 at Taleghani Pediatric Hospital in Gorgan, Iran. RESULT: The average age was 18.8 ± 30.3 months, with the majority being boys (62.5%). Most participants had CCAM (41.7%), followed by CLE (18.1%), BPS (16.7%), pulmonary hypoplasia (9.7%), BC (8.3%), and hybrid lesion (5.6%). The majority of patients were Fars (62.5%), and the average hospitalization days was 9.4 ± 4.5 days. Cardiac anomalies were observed in 19.4% of the patients. 62 patients (86.1%) exhibited respiratory symptoms, and prenatal screening during pregnancy led to the diagnosis in 51 patients (70.8%). Most patients had left lung anomalies (43; 59.7%), and the majority (90.3%) survived. There is a statistically significant relation between needed for surgical treatment and patients' type of pulmonary lesions (p-value: 0.02). In addition, there was a significant relation between the Fars ethnicity and the presence of cardiac anomalies (p-value: 0.04). CONCLUSION: Some CLAs remain undiagnosed or untreated due to the rare nature of congenital lung anomalies. Nevertheless, improvements in ultrasound and other imaging methods will make diagnosing and managing these anomalies during the prenatal period more prevalent, resulting in enhanced understanding.

Comparison of ICG-Guided Near-Infrared Fluorescence Imaging and Modified Inflation-Deflation Method in Identifying the Intersegmental Plane During Lung Segmentectomy of Infants.

BACKGROUND: The identification of the intersegmental plane (ISP) is a crucial step in segmentectomy for children with congenital pulmonary airway malformation (CPAM) due to complex anatomical variations. However, there is very limited literature available on this aspect specifically for infant. In this study, we compared the intravenous indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) imaging method with the modified inflation-deflation method in terms of their perioperative characteristics and summarized our experience. METHODS: From June 2021 to November 2022, the data of 83 patients with CPAM who underwent segmentectomy by video-assisted thoracoscopic surgery were retrospectively reviewed. Twenty-eight patients underwent ICG-guided NIRF method, and 56 patients underwent the modified inflation-deflation method, characteristics and clinical outcomes were compared. RESULTS: The median age of the patients was 4.99 months (4.99 ± 1.51) with a mean body weight of 7.54 kg (7.54 ± 1.99). Both methods could accurately identify the ISP. The time taken to clearly display the ISP was shorter in ICG group than in the modified inflation-deflation group (0.18 ± 0.08 vs. 6.49 ± 1.67 min; P < 0.001), and the surgical duration (61.32 ± 14.28 vs. 88.18 ± 8.03 min; P < 0.001) were significantly shorter in the ICG group too. The two groups exhibited differences in the length of chest tube drainage (1.75 ± 1.24 vs. 2.36 ± 1.54 days; P = 0.072) and the length of hospital stay (4.61 ± 1.75 vs. 5.20 ± 3.07 days; P = 0.078), however, the differences were not statistically significant. There were no significant differences between the two groups in the blood lost and postoperative complications. At a follow-up of more than 1 year after operation, all patients had recovered well without recurrence. CONCLUSIONS: According to our experience, the ICG-guided NIRF method was safe and feasible for infants during thoracoscopic segmentectomy, it can quickly display the ISP and shorten the surgical duration compared with the modified inflation-deflation method.

Antenatally Detected Thoracic Lesions: Prognosis, Management and Outcome.

BACKGROUND: Foetal thoracic lesions are uncommon, with the incidence of 1 in 15,000 live births. Antenatal monitoring of these lesions is required to prognosticate the parents about the postnatal outcome of the lesions and about the well-being of the baby. Foetal ultrasound and magnetic resonance imaging (MRI) are the modalities to detect these lesions and follow-up during pregnancy and postnatally. Congenital pulmonary adenomatoid malformations (CPAM), congenital diaphragmatic hernia (CDH) and bronchopulmonary sequestrations (BPS) are the commonly detected foetal thoracic lesions. Parameters such as congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) and lung-to-head ratio (LHR) determine the prognosis of these lesions. With this background, we planned to study the prognosis and outcome of antenatally detected thoracic lesions. MATERIALS AND METHODS: This was a prospective study carried out for 2 years (January 2017 to December 2018). Pregnant females with foetuses diagnosed to have thoracic lesions on the second- and third-trimester ultrasound and foetal MRI were enrolled for the study. CVR and LHR were noted. Outcomes were analysed in terms of the need of termination of pregnancy, foetal or neonatal demise and need of surgery or conservative management. RESULTS: Of a total of 521 pregnancies, thoracic lesions were detected in 22 (4.22%) cases. Individually, the incidence of each lesion was: CPAM-10 (45.45%), BPS-5 (22.73%), CDH-5 (22.73%) and congenital higher airway obstruction-2 (9.1%). Chromosomal screening was normal in 100% of cases. Follow-up was done for 2 years. Termination of pregnancy was required in 3 (13.64%) cases, postnatal death occurred in 4 (18.2%) cases, surgery was required in three cases of CDH soon after birth and two cases of extralobar BPS at 2 years of age. 10 (45.45%) cases were managed conservatively, who are doing well at 2-year follow-up. CONCLUSION: CPAMs, BPSs and CDH are the commonly detected antenatal thoracic lesions. Ultrasonography and MRI help detect and prognosticate the parents about the outcomes of these lesions. CVR and LHR with associated congenital malformations are important prognostic markers for these lesions. There is a need of long-term prospective studies to delineate the natural history of these lesions.

Efficacy of Da Vinci Robot-assisted Thoracoscopic Surgery in Children With Congenital Cystic Adenomatiod Malformation.

BACKGROUND: Surgical intervention is advisable for both asymptomatic and symptomatic CCAM children. This study aims to compare and analyze the efficacy of thoracoscopic and Da Vinci robot-assisted procedures in the management of CCAM among pediatric patients. METHODS: The clinical data of 188 pediatric patients diagnosed with CCAM and admitted to the Children's Hospital, Zhejiang University School of Medicine, from April 2019 to April 2023 were retrospectively analyzed. The Clavien-Dindo classification was employed for the systematic categorization of postoperative complications. RESULTS: The demographic and clinical characteristics of the patients were comparable between the two groups. Postoperative outcomes, such as the chest tube indwelling rate (92.6% vs 36.2%, p < 0.001∗), chest tube duration (2.0 (2.0-3.0) days vs 1.0 (1.0-2.0) days, p < 0.001∗), and length of postoperative hospital stay (6.0 (5.0-7.0) days vs 5.0 (5.0-6.0) days, p < 0.001∗), favored RATS over VATS. Additionally, there was no significant difference in complications between the two group, but the p-value is in a critical state. Ⅲa complications (mainly composed of postoperative thoracentesis procedures) manifesting as a higher rate in the RATS, nearly double that observed in the VATS. CONCLUSIONS: Robot-assisted thoracoscopic lung resection is demonstrated to be safe and feasible, with notable advantages in short-term postoperative clinical outcomes. Nevertheless, the practicality and long-term benefits of this technique necessitate further refinement and dedicated study. LEVEL OF EVIDENCE: LEVEL III.

The underlying molecular mechanism of ciliated epithelium dysfunction and TGF-ß signaling in children with congenital pulmonary airway malformations.

The aim of this study was to investigate the variation in gene expression in the complete transcripts of Congenitalpulmonary airwaymalformation (CPAM) of the lung using Next Generation Sequencing (NGS) technology. There were 20 cases involving children with CPAM were used for selection of study sample. NGS was used to establish RNA-Seq libraries for the two groups of samples separately, and both groups were conducted to differential expression analysis and Gene Ontology (GO) functional enrichment analysis. The pathways of the differential genes were analyzed to find the enriched target pathways. A total of 592 genes were expressed with significant differences (CPAM vs. normal tissue, P < 0.05). GO functional analysis of DEGs indicated that abnormal ciliary function played a role in the development of CPAM. Subsequently, analysis of these genes pathways showed the TGF-ß signaling pathway was significantly enriched. Finally, the results of immunohistochemical analysis of some DEGs showed that a significant reduction in the expression of SMAD6, a gene related to the TGF-ß signaling pathway, led to abnormal activation of the pathway. TGF-ß signaling pathway involved in the evolution of the disease obtained by DEGs enrichment pathway analysis. SMAD6, a gene involved in this pathway, might be a potential biomarker for the diagnosis and treatment of CPAM.

Complicated Congenital Pulmonary Adenomatoid Malformation Type I following Right Lower Lobectomy: A Case Report.

Congenital pulmonary airway malformation is a rare congenital abnormality of the lungs. It can manifest at any age and can lead to significant morbidity and mortality in infants and children. Some individuals with congenital lung malformations may present with respiratory symptoms right after birth, while others may remain asymptomatic for extended periods. We present a case of a 4-year-old female child who experienced recurrent chest infections. Imaging revealed type I congenital pulmonary airway malformation with an underlying infection. Despite the increased risks associated with surgery and the complexity of the disease, the patient underwent a posterolateral thoracotomy with resection of the right lower lobe. The patient achieved successful outcomes and was able to recover successfully following the surgery. This case study holds significance because several studies have focused on the timing and outcomes of surgical intervention in asymptomatic cases, there remains a lack of consensus regarding symptomatic patients and their outcomes after surgery. Keywords: case reports; neonates; pneumonia.

[Clinicopathological and genetic characteristics of congenital cystic adenomatoid malformation of lung and its associated lung cancer in adults].

Objective: To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults. Methods: A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases. Results: The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene. Conclusions: CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.

Assessment of mediastinal shift angles in congenital pulmonary airway malformation: a new fetal magnetic resonance imaging indicator of congenital lung disease.

BACKGROUND: The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. OBJECTIVE: This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. MATERIALS AND METHODS: To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. RESULTS: The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). CONCLUSION: The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM in fetal MRI.

Respiratory and Musculoskeletal Long-Term Outcomes after Surgical Resection of Congenital Cystic Adenomatoid Malformation of the Lung in Newborns, Infants, and Toddlers.

INTRODUCTION: The long-term outcomes of children who underwent surgery for congenital cystic adenomatoid malformation of the lung (CCAML) are not well documented, particularly regarding orthopaedic and respiratory follow-up (FU). The aim of this study was to assess the long-term pulmonary and orthopaedic outcomes of surgically treated CCAML in newborns, infants, and toddlers. MATERIALS AND METHODS: Retrospective examination of prospectively recorded data of consecutive patients with CCAML who underwent surgery at our tertiary referral institution from January 2000 to December 2015 (newborns, infants, and toddlers). Clinical, radiological, and surgical data, as well as FU data were revised. A multidisciplinary team followed the patients after discharge at scheduled time points. RESULTS: Seventy-seven patients were included. After surgery, patients were followed for a median of 8 years (range: 1-19 years) until they reached a median age of 8 years (range: 2-19 years). Thirty patients (39%) developed wheezing and 21 (27%) had lower respiratory tract infections (LRTIs) within 4 years of age. However, more than 50% of patients with respiratory symptoms underwent complete remission in the following 4 years. Thirty-one patients (40%) developed at least one minimal musculoskeletal deformity. Eighteen (23%) had scoliosis, 17 (22%) thoracic asymmetry, 10 (12%) pectus excavatum, and 5 (6%) winged scapula. CONCLUSIONS: Patients operated for CCAML had good overall outcomes despite pulmonary symptoms and musculoskeletal sequelae. Even though these issues are frequently paucisymptomatic, trying to use less-invasive procedures (such as minimally axillary open "muscle-sparing" thoracotomy or thoracoscopy) may reduce this burden. A structured multidisciplinary FU is required.

No Pathogenic DICER1 Gene Variants in a Cohort Study of 28 Children With Congenital Pulmonary Airway Malformation.

BACKGROUND: Distinguishing congenital pulmonary airway malformations (CPAMs) from pleuropulmonary blastoma (PPB) can be challenging. Previously diagnosed patients with CPAM may have been misdiagnosed and we may have missed DICER1-associated PPBs, a diagnosis with important clinical implications for patients and their families. To gain insight in potential misdiagnoses, we systematically assessed somatic DICER1 gene mutation status in an unselected, retrospective cohort of patients with a CPAM diagnosis. METHODS: In the Amsterdam University Medical Center (the Netherlands), it has been standard policy to resect CPAM lesions. We included all consecutive cases of children (age 0-18 years) with a diagnosis of CPAM between 2007 and 2017 at this center. Clinical and radiographic features were reviewed, and DICER1 gene sequencing was performed on DNA retrieved from CPAM tissue samples. RESULTS: Twenty-eight patients with a surgically removed CPAM were included. CPAM type 1 and type 2 were the most common subtypes (n = 12 and n = 13). For 21 patients a chest CT scan was available for reassessment by two pediatric radiologists. In 9 patients (9/21, 43%) the CPAM subtype scored by the radiologists did not correspond with the subtype given at pathology assessment. No pathogenic mutations and no copy number variations of the DICER1 gene were found in the DNA extracted from CPAM tissue (0/28). CONCLUSIONS: Our findings suggest that the initial CPAM diagnoses were correct. These findings should be validated through larger studies to draw conclusions regarding whether systematic DICER1 genetic testing is required in children with a pathological confirmed diagnosis of CPAM or not. LEVEL OF EVIDENCE: Level IV.

A ten-year review of congenital pulmonary airway malformation cases in a pediatric tertiary hospital

Objective@#A retrospective study of the demographic, clinical and diagnostic profile, intervention and outcomes of children with Congenital Pulmonary Airway Malformation (CPAM) in Philippine Children’s Medical Center (PCMC) from January 2011 to December 2021 was presented.@*Methodology@#Medical charts of identified patients were reviewed. Data obtained included demographic profile, clinical history, diagnostic procedures, intervention, and outcomes. The findings were analyzed and correlated with the synthesized findings from relevant studies about CPAM.@*Results@#Twenty-three cases (n=23) were included in the study. Most of the patients were diagnosed at 1 to 11 months of age, accounting for 43.48% while there is a minimal disparity in terms of gender distribution. Seventy-five percent of neonates presented with respiratory distress while recurrent pneumonia occurred more frequently beyond the neonatal period. Four patients at 17.39% had incidental findings of CPAM on prenatal ultrasound. All cases were confirmed using a Chest CT scan and only six patients at 26.09% had Chest X-ray results consistent with CPAM. Eight cases were confirmed using biopsy wherein results were mainly Type I seen in 87.5% of cases. Lobectomy is the procedure of choice with 92.86% success rate. Overall, patients who underwent surgical intervention had a low complication rate at 6.25%. @*Conclusion@#CPAM is most common in patients aged 1 to 11 months and has no gender predilection. Neonates often present with respiratory distress while recurrent pneumonia is the most common clinical manifestation beyond neonatal period. CPAM can be detected using ultrasound prenatally and CT scan can confirm CPAM postnatally. Surgical intervention particularly lobectomy is the preferred option over conservative management which showed a favorable outcome. CPAM has an overall good prognosis. Findings of this research may guide clinicians in the diagnosis and management of CPAM in the Philippines.

Rare presentation of pneumothorax in a young woman with underlying congenital pulmonary airway malformation.

Congenital pulmonary airway malformation (CPAM) is the most common among a rare group of congenital anomalies of the lower respiratory tract. It has variable presentation depending on its subtype and the patient's age. It may lead to respiratory distress in neonates. It can be a particularly challenging diagnosis in children born asymptomatic but present with complications later in life such as haemoptysis, recurrent chest infections, breathlessness and pneumothorax. Prenatal ultrasound, chest X-ray, CT scan and MRI are helpful in making a radiological diagnosis.A woman in her late teens presented with shortness of breath and right pleuritic chest pain. CT's chest showed a number of bullae of varying sizes on the right, including one huge bulla compressing all three lobes. She underwent lung volume reduction surgery via video-assisted thoracoscopy, and the histology specimen confirmed the diagnosis of CPAM type 1.

Selection of potential targets for stratifying congenital pulmonary airway malformation patients with molecular imaging: is MUC1 the one?

Currently there is a global lack of consensus about the best treatment for asymptomatic congenital pulmonary airway malformation (CPAM) patients. The somatic KRAS mutations commonly found in adult lung cancer combined with mucinous proliferations are sometimes found in CPAM. For this risk of developing malignancy, 70% of paediatric surgeons perform a resection for asymptomatic CPAM. In order to stratify these patients into high- and low-risk groups for developing malignancy, a minimally invasive diagnostic method is needed, for example targeted molecular imaging. A prerequisite for this technique is a cell membrane bound target. The aim of this study was to review the literature to identify potential targets for molecular imaging in CPAM patients and perform a first step to validate these findings.A systematic search was conducted to identify possible targets in CPAM and adenocarcinoma in situ (AIS) patients. The most interesting targets were evaluated with immunofluorescent staining in adjacent lung tissue, KRAS+ CPAM tissue and KRAS- CPAM tissue.In 185 included studies, 143 possible targets were described, of which 20 targets were upregulated and membrane-bound. Six of them were also upregulated in lung AIS tissue (CEACAM5, E-cadherin, EGFR, ERBB2, ITGA2 and MUC1) and as such of possible interest. Validating studies showed that MUC1 is a potential interesting target.This study provides an extensive overview of all known potential targets in CPAM that might identify those patients at risk for malignancy and conducted the first step towards validation, identifying MUC1 as the most promising target.

Congenital lung malformations.

Congenital lung malformations (CLMs) are rare developmental anomalies of the lung, including congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and isolated congenital bronchial atresia. CLMs occur in 4 out of 10,000 live births. Postnatal presentation ranges from an asymptomatic infant to respiratory failure. CLMs are typically diagnosed with antenatal ultrasonography and confirmed by chest CT angiography in the first few months of life. Although surgical treatment is the gold standard for symptomatic CLMs, a consensus on asymptomatic cases has not been reached. Resection, either thoracoscopically or through thoracotomy, minimizes the risk of local morbidity, including recurrent infections and pneumothorax, and avoids the risk of malignancies that have been associated with CPAM, bronchopulmonary sequestration and bronchogenic cyst. However, some surgeons suggest expectant management as the incidence of adverse outcomes, including malignancy, remains unknown. In either case, a planned follow-up and a proper transition to adult care are needed. The biological mechanisms through which some CLMs may trigger malignant transformation are under investigation. KRAS has already been confirmed to be somatically mutated in CPAM and other genetic susceptibilities linked to tumour development have been explored. By summarizing current progress in CLM diagnosis, management and molecular understanding we hope to highlight open questions that require urgent attention.

Treatment of congenital pulmonary airway malformation with rare high cystic volume ratio: A case report and literature review.

RATIONALE: Congenital pulmonary airway malformation (CPAM) is a rare congenital dysplastic malformation and accounts for 25% of congenital lung lesions. Commonly, it is diagnosed prenatally in ultrasound. The CPAM volume ratio (CVR) is a well-recognized predictor of fetal prognosis, and when the CVR is >1.6 cm2, the fetus is very likely to develop hydrops and even intrauterine deaths. However, the association of CVR with a wide range of complications and neonatal prognosis is unclear. PATIENT CONCERNS: Cystic lesions in the right thorax of the fetus detected by ultrasound at 19 weeks of gestation, with a CVR of 0.88 cm2. The CVR grew progressively with increasing gestational weeks, reaching a maximum of 5.2 cm2 at 35 gestational weeks. However, there were no complications with the fetus other than polyhydramnios. DIAGNOSIS: Imaging and pathological findings confirmed the diagnosis of CPAM. INTERVENTIONS: During pregnancy, a multidisciplinary team was involved in the management and the prenatal visits increased to weekly from 31 weeks of gestation. During the cesarean section, neonatologists and pediatric surgeons were present for timely evaluation of newborns. The neonate was admitted to the neonatal intensive care unit for monitoring immediately after birth and underwent thoracoscopic right lower lobectomy at 57th days old. OUTCOMES: The neonate recovered without any respiratory symptoms and no abnormality on chest computed tomography (CT) at the 3-month postoperative follow-up. LESSONS: During pregnancy, in addition to monitoring CVR, a multidisciplinary team should join in the management of CPAM patients. And as for the fetus with increased CVR, a closely monitoring after birth is necessary even if the general condition of the pregnancy is well. In particular, timely intervention should be made at the onset of respiratory symptoms.

Prenatally Diagnosed Large Lung Lesions: Timing of Resection and Perinatal Outcomes.

INTRODUCTION: Fetuses with large lung lesions including congenital cystic adenomatoid malformations (CCAMs) are at risk for cardiopulmonary compromise. Prenatal maternal betamethasone and cyst drainage for micro- and macrocystic lesions respectively have improved outcomes yet some lesions remain large and require resection before birth (open fetal surgery, OFS), at delivery via an Ex Utero Intrapartum Treatment (EXIT), or immediately post cesarean section (section-to-resection, STR). We sought to compare prenatal characteristics and outcomes in fetuses undergoing OFS, EXIT, or STR to inform decision-making and prenatal counseling. METHODS: A single institution retrospective review was conducted evaluating patients undergoing OFS, EXIT, or STR for prenatally diagnosed lung lesions from 2000 to 2021. Specimens were reviewed by an anatomic pathologist. Lesions were divided into "CCAMs" (the largest pathology group) and "all lung lesions" since pathologic diagnosis is not possible during prenatal evaluation when care decisions are made. Prenatal variables included initial, greatest, and final CCAM volume-ratio (CVR), betamethasone use/frequency, cyst drainage, and the presence of hydrops. Outcomes included survival, ECMO utilization, NICU length of stay (LOS), postnatal nitric oxide use, and ventilator days. RESULTS: Sixty-nine percent (59 of 85 patients) of lung lesions undergoing resection were CCAMs. Among patients with pathologic diagnosis of CCAM, the initial, largest, and final CVRs were greatest in OFS followed by EXIT and STR patients. Similarly, the incidence of hydrops was significantly greater and the rate of hydrops resolution was lower in the OFS group. Although the rate of cyst drainage did not differ between groups, maternal betamethasone use varied significantly (OFS 60.0%, EXIT 100.0%, STR 74.3%; p = 0.0378). Notably, all OFS took place prior to 2014. There was no difference in survival, ventilator days, nitric oxide, NICU LOS, or ECMO between groups. In multiple variable logistic modeling, determinants of survival to NICU discharge among patients undergoing resection with a pathologic diagnosis of CCAM included initial CVR <3.5 and need for <3 maternal betamethasone doses. CONCLUSION: For CCAMs that remain large despite maternal betamethasone or cyst drainage, surgical resection via OFS, EXIT, or STR are viable options with favorable and comparable survival between groups. In the modern era there has been a shift from OFS and EXIT procedures to STR for fetuses with persistently large lung lesions. This shift has been fueled by the increased use of maternal betamethasone and introduction of a Special Delivery Unit during the study period and the appreciation of similar fetal and neonatal outcomes for STR vs. EXIT and OFS with reduced maternal morbidity associated with a STR. Accordingly, efforts to optimize multidisciplinary perinatal care for fetuses with large lung lesions are important to inform patient selection criteria and promote STR as the preferred surgical approach in the modern era. LEVEL OF EVIDENCE: Level IV.

Serial lung mass volume ratios as prognostic indicators of neonatal respiratory morbidity in fetal pulmonary malformations.

BACKGROUND: Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids. OBJECTIVE: This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations. STUDY DESIGN: This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O2 at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05). RESULTS: There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm2 at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm2 at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm2 at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm2, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm2, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm2 with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period. CONCLUSION: Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm2 are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.